Gold trifluoromethyl complexes as efficient regioselective catalysts in alkyne hydration.

Gold (III) complexes containing trifluromethyl ligands are efficient catalyst in the hydration of alkynes, operating at low catalyst loadings, without additives, using environmentally friendly solvents and at mild conditions (60 ºC). Hydration of terminal and internal alkynes provide the corresponding ketones in quantitative yields without special precautions as dry solvents or inert atmospheres. Remarkably, hydration of asymmetric internal alkynes proceeds with moderate to notable regioselectivities, providing mixtures of the two possible isomers with ratios up to 90:10.

Value contribution of cenobamate for the treatment of Focal-Onset Seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through reflective Multi-Criteria Decision Analysis (MCDA).

INTRODUCTION: Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti-seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the decision to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribution of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. PURPOSE: The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA-based methodology. METHODS: A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA framework adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improvements in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (excluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high therapeutic impact and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA methodology and stakeholders' experience in clinical management of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs.

Engaging Same-Day Peer Ambassadors to Increase Coronavirus Disease 2019 Vaccination Among People Experiencing Unsheltered Homelessness in Los Angeles County: A Hybrid Feasibility-Evaluation Study.

BACKGROUND: This study aimed to evaluate the feasibility and acceptability of engaging unhoused peer ambassadors (PAs) in coronavirus disease 2019 (COVID-19) vaccination efforts to reach people experiencing unsheltered homelessness in Los Angeles County. METHODS: From August to December 2021, vaccinated PAs aged ≥18 years who could provide informed consent were recruited during vaccination events for same-day participation. Events were held at encampments, service providers (eg, housing agencies, food lines, and mobile showers), and roving locations around Los Angeles. PAs were asked to join outreach alongside community health workers and shared their experience getting vaccinated, receiving a $25 gift card for each hour they participated. Postevent surveys evaluated how many PAs enrolled and how long they participated. In October 2021, we added a preliminary effectiveness evaluation of how many additional vaccinations were attributable to PAs. Staff who enrolled the PAs estimated the number of additional people vaccinated because of talking with the PA. RESULTS: A total of 117 PAs were enrolled at 103 events, participating for an average of 2 hours. At events with the effectiveness evaluation, 197 additional people were vaccinated over 167 PA hours ($21.19 gift card cost per additional person vaccinated), accounting for >25% of all vaccines given at these events. DISCUSSION: Recruiting same-day unhoused PAs is a feasible, acceptable, and preliminarily effective technique to increase COVID-19 vaccination in unsheltered settings. The findings can inform delivery of other health services for people experiencing homelessness.

Phenotypic selection on an ornamental trait is not modulated by breeding density in a pied flycatcher population.

Most studies of phenotypic selection in the wild have focussed on morphological and life-history traits and looked at abiotic (climatic) variation as the main driver of selection. Consequently, our knowledge of the effects of biotic environmental variation on phenotypic selection on sexual traits is scarce. Population density can be considered a proxy for the intensity of intrasexual and intersexual competition and could therefore be a key factor influencing the covariation between individual fitness and the expression of sexual traits. Here, we used an individual-based data set from a population of pied flycatchers (Ficedula hypoleuca) monitored over 24 years to analyze the effect of breeding density on phenotypic selection on dorsal plumage colouration, a heritable and sexually selected ornament in males of this species. Using the number of recruits as a fitness proxy, our results showed overall stabilizing selection on male dorsal colouration, with intermediate phenotypes being favoured over extremely dark and dull individuals. However, our results did not support the hypothesis that breeding density mediates phenotypic selection on this sexual trait. We discuss the possible role of other biotic factors influencing selection on ornamental plumage.

The contribution of fenfluramine to the treatment of Dravet syndrome in Spain through Multi-Criteria Decision Analysis.

INTRODUCTION: Dravet Syndrome (DS) is a severe, developmental epileptic encephalopathy (DEE) that begins in infancy and is characterized by pharmaco-resistant epilepsy and neurodevelopmental delay. Despite available antiseizure medications (ASMs), there is a need for new therapeutic options with greater efficacy in reducing seizure frequency and with adequate safety and tolerability profiles. Fenfluramine is a new ASM for the treatment of seizures associated with DS as add-on therapy to other ASMs for patients aged 2 years and older. Fenfluramine decreases seizure frequency, prolongs periods of seizure freedom potentially helping to reduce risk of Sudden Unexpected Death in Epilepsy (SUDEP) and improves patient cognitive abilities positively impacting on patients' Quality of Life (QoL). Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. The aim of this study was to determine the relative value contribution of fenfluramine for the treatment of DS in Spain using MCDA. METHOD: A literature review was performed to populate an adapted a MCDA framework for orphan-drug evaluation in Spain. A panel of ten Spanish experts, including neurologists, hospital pharmacists, patient representatives and decision-makers, scored four comparative evidence matrices. Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: Dravet syndrome is considered a severe, rare disease with significant unmet needs. Fenfluramine is perceived to have a higher efficacy profile than all available alternatives, with a better safety profile than stiripentol and topiramate and to provide improved QoL versus studied alternatives. Fenfluramine results in lower other medical costs in comparison with stiripentol and clobazam. Participants perceived that fenfluramine could lead to indirect costs savings compared to available alternatives due to its efficacy in controlling seizures. Overall, fenfluramine's therapeutic impact on patients with DS is considered high and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA, fenfluramine is considered to add greater benefit in terms of efficacy, safety and QoL when compared with available ASMs.

Improving Catalyst Activity in Hydrocarbon Functionalization by Remote Pyrene-Graphene Stacking.

A copper complex bearing an N-heterocyclic carbene ligand with a pyrene "tail" attached to the backbone has been prepared and supported on reduced graphene oxide (rGO). The free and supported copper materials have been employed as homogeneous and heterogeneous catalysts in the functionalization of hydrocarbons such as n-hexane, cyclohexane, and benzene through incorporation of the CHCO2 Et unit from ethyl diazoacetate. The graphene-anchored complex displays higher reaction rates and induces higher yields than its soluble counterpart, features that can be rationalized in terms of a decrease in electron density at the metal center due to a remote net electronic flux from the supported copper complex to the graphene surface.

Reduction of the Measurement Time by the Prediction of the Steady-State Response for Quartz Crystal Microbalance Gas Sensors.

This paper presents a new approach to reduce the measurement time by the prediction of the steady-state using the transient response to ethanol for quartz crystal microbalance gas sensors coated with ethyl cellulose. The experimentally measured response curves were successively fitted using a mathematical model based on the sum of two exponentials with different time constants. The parameters of the model were determined, and the time constants and the magnitude of the steady-state response were analyzed. Even though the time constants did not stabilize well, the parameter corresponding to the magnitude of the steady-state response quickly converged and stabilized after 37 s. Moreover, this calculated parameter was highly correlated with the measured values of the steady-state response, which was measured at five times the longest time constant (83 s) of the model. Therefore, the steady-state response could be predicted with a 55% reduction in the measurement (detection) time.

Catalytic Dehydrogenative Coupling of Hydrosilanes with Alcohols for the Production of Hydrogen On-demand: Application of a Silane/Alcohol Pair as a Liquid Organic Hydrogen Carrier.

The compound [Ru(p-cym)(Cl)2 (NHC)] is an effective catalyst for the room-temperature coupling of silanes and alcohols with the concomitant formation of molecular hydrogen. High catalyst activity is observed for a variety of substrates affording quantitative yields in minutes at room temperature and with a catalyst loading as low as 0.1 mol %. The coupling reaction is thermodynamically and, in the presence of a Ru complex, kinetically favourable and allows rapid molecular hydrogen generation on-demand at room temperature, under air, and without any additive. The pair silane/alcohol is a potential liquid organic hydrogen carrier (LOHC) for energy storage over long periods in a safe and secure way. Silanes and alcohols are non-toxic compounds and do not require special handling precautions such as high pressure or an inert atmosphere. These properties enhance the practical applications of the pair silane/alcohol as a good LOHC in the automotive industry. The variety and availability of silanes and alcohols permits a pair combination that fulfils the requirements for developing an efficient LOHC.

Are there intra-operative hemodynamic differences between the Coliseum and closed HIPEC techniques in the treatment of peritoneal metastasis? A retrospective cohort study.

BACKGROUND: Although two main methods of intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) are currently accepted, the superiority of one over the other has not yet been demonstrated. The purpose of this study was to determine whether there are hemodynamic and temperature differences between patients who received HIPEC in two different techniques, open versus closed abdomen. METHODS: This retrospective study was conducted in our center between 2011-2015 in 30 patients who underwent surgery for peritoneal carcinomatosis secondary to colorectal cancer, in whom cytoreduction and HIPEC were performed by the Coliseum (15) or closed techniques (15). The main end points were morbidity, mortality, hemodynamic changes, and abdominal temperature. The comparative analysis of quantitative variables at different times was done with the parametric repeated measure ANOVA for those variables that fulfilled the suppositions of normality and independence and the Friedman non-parametric test for the variables that did not fulfill either of these suppositions. RESULTS: There were no deaths in either group. The incidence of postoperative complications in the Coliseum group was 53% (8 patients), grade II-III. The incidence of complications in the closed group was 13% (2 patients), grade II-III. The intra-operative conditions regarding the systolic and diastolic pressures were more stable using the closed abdomen technique (but not significantly so). We found statistically significant differences in abdominal temperature in favor of the closed technique (p = 0.009). CONCLUSIONS: Both HIPEC procedures are similar. In our series, the closed technique resulted in a more stable intra-abdominal temperature.

Which unscheduled return visits indicate a quality-of-care issue?

BACKGROUND: The rate of unscheduled return visits is often used as a quality-of-care indicator in EDs, although its validity is not yet fully established. Our aim was to identify the characteristics of return visits that may be attributed to problems in quality of care. METHODS: Retrospective paired review of medical charts in a random sample of return visits during the 72 hours following discharge from the ED in three hospitals of Andalusia, Spain in 2013. Charts were reviewed by senior medical physicians to determine which return visits reflected quality-of-care problems. Time frame for return visit, index and return visit acuity, disposition and diagnosis were compared with determine which variables were associated with a quality problem. Sensitivity and specificity for each variable to indicate a quality problem were determined. RESULTS: We studied the causes of 895 return visits, finding that 65 (7.3%) were due to inadequate quality of care in the index visit. Potentially avoidable return visits were more common in more severely ill patients, in those with greater severity in the return than in the index visit and in patients hospitalised after the return. The combination of this three variables presented sensitivity 66% and specificity 68% in identification of quality-related returns. CONCLUSIONS: The overall level of return visits cannot be considered a valid indicator of quality of care. However, certain specific variables, including the level of severity of the patient's condition or the discharge destination following the return visits, could be considered valid in this respect.

[Psychopathology screening in medical school students]. / Sistema de tamizaje de psicopatología en estudiantes de Medicina.

OBJECTIVE: Screening of psychopathology and associated factors in medical students employing an electronic self-report survey. METHOD: A transversal, observational, and comparative study that consisted of the following instruments: Sociodemographic survey; 2. Adult Self-Report Scale-V1 (ASRS); State-Trait Anxiety Inventory (STAI); Zung and Conde Self-Rating Depression Scale, Almonte-Herskovic Sexual Orientation Self-Report; Plutchik Suicide Risk Scale; Alcohol Use Disorders Identification Test Identification (AUDIT); Fagerström Test for Nicotine Dependence; 9. Maslach Burnout Inventory (MBI); Eating Disorder Inventory 2 (EDI). RESULTS: We gathered 323 student surveys from medical students of the first, third and sixth grades. The three more prevalent disorders were depression (24%), attention deficit disorders with hyperactivity (28%) and anxiety (13%); the prevalence of high-level burnout syndrome was 13%. Also, the fifth part of the students had detrimental use of tobacco and alcohol. CONCLUSION: Sixty percent of medical students had either one or more probable disorder or burnout. An adequate screening and treatment of this population could prevent severe mental disorders and the associated factors could help us to create a risk profile. This model is an efficient research tool for screening and secondary prevention.

Catalytic Hydrogen Production by Ruthenium Complexes from the Conversion of Primary Amines to Nitriles: Potential Application as a Liquid Organic Hydrogen Carrier.

The potential application of the primary amine/nitrile pair as a liquid organic hydrogen carrier (LOHC) has been evaluated. Ruthenium complexes of formula [(p-cym)Ru(NHC)Cl2 ] (NHC=N-heterocyclic carbene) catalyze the acceptorless dehydrogenation of primary amines to nitriles with the formation of molecular hydrogen. Notably, the reaction proceeds without any external additive, under air, and under mild reaction conditions. The catalytic properties of a ruthenium complex supported on the surface of graphene have been explored for reutilization purposes. The ruthenium-supported catalyst is active for at least 10 runs without any apparent loss of activity. The results obtained in terms of catalytic activity, stability, and recyclability are encouraging for the potential application of the amine/nitrile pair as a LOHC. The main challenge in the dehydrogenation of benzylamines is the selectivity control, such as avoiding the formation of imine byproducts due to transamination reactions. Herein, selectivity has been achieved by using long-chain primary amines such as dodecylamine. Mechanistic studies have been performed to rationalize the key factors involved in the activity and selectivity of the catalysts in the dehydrogenation of amines. The experimental results suggest that the catalyst resting state contains a coordinated amine.

Pharmaceutical cost management in an ambulatory setting using a risk adjustment tool.

BACKGROUND: Pharmaceutical expenditure is undergoing very high growth, and accounts for 30% of overall healthcare expenditure in Spain. In this paper we present a prediction model for primary health care pharmaceutical expenditure based on Clinical Risk Groups (CRG), a system that classifies individuals into mutually exclusive categories and assigns each person to a severity level if s/he has a chronic health condition. This model may be used to draw up budgets and control health spending. METHODS: Descriptive study, cross-sectional. The study used a database of 4,700,000 population, with the following information: age, gender, assigned CRG group, chronic conditions and pharmaceutical expenditure. The predictive model for pharmaceutical expenditure was developed using CRG with 9 core groups and estimated by means of ordinary least squares (OLS). The weights obtained in the regression model were used to establish a case mix system to assign a prospective budget to health districts. RESULTS: The risk adjustment tool proved to have an acceptable level of prediction (R2 ≥ 0.55) to explain pharmaceutical expenditure. Significant differences were observed between the predictive budget using the model developed and real spending in some health districts. For evaluation of pharmaceutical spending of pediatricians, other models have to be established. CONCLUSION: The model is a valid tool to implement rational measures of cost containment in pharmaceutical expenditure, though it requires specific weights to adjust and forecast budgets.

Ion mobility mass spectrometry uncovers regioselectivity in the carboxylate-assisted C-H activation of palladium N-heterocyclic carbene complexes.

Carboxylate-assisted Pd-catalyzed C-H bond activation constitutes a mild and versatile synthetic tool to efficiently and selectively cleave inert C-H bonds. Herein, we demonstrate a simple method to experimentally evaluate both reactivity and selectivity in such systems using mass spectrometry (MS) methods. The N-heterocyclic carbene (NHC) cations [(NHC)PdX]+, bearing as X- ligand bases commonly used to promote the C-H activation (carboxylates and bicarbonate), are generated in the gas-phase by ESI-MS. Their C-H bond activation at the N-bound groups of the NHC is then studied using Collision Induced Dissociation (CID) experiments. Ion Mobility Spectrometry (IM)-MS is exploited to identify a number of regioisomers associated with the distinctive site selective C-H activations. It is demonstrated that such C-H activation concomitant with acetic acid release occurs from a mixture of activated [(NHC-H)Pd(CH3CO2H)]+ and non-activated [(NHC)Pd(CH3CO2)]+ complexes. The identity of the X-type ligands (X = Cl-, carboxylates and bicarbonate) has a significant impact on the regioisomer branching ratio upon CID conditions. IM-MS in conjunction with a DFT mechanistic study is presented for the acetate-assisted C-H activation of the [(NHC)Pd(CH3CO2)]+ cation featuring butyl and aryl as N-donor groups.

Targeted axillary dissection using Radioguided Occult Lesion Localization technique in the clinically negative marked lymph node after neoadjuvant treatment in breast cancer patients.

PURPOSE: To be aware of the feasibility of targeted axillary dissection (TAD) injecting 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA) preoperatively into the clipped lymph node of patients with axillary complete clinical response (ycN0), after neoadjuvant chemotherapy (NAC) for breast cancer. PATIENTS AND METHODS: A retrospective observational study was performed on N1 patients with a clipped positive node and a clinically negative axilla (ycN0) after NAC in one center. The pretreatment positive lymph node was injected with 99mTc-MAA the day before surgery and identified intraoperatively with a radioguided occult lesion localization (ROLL) technique. Patients were subjected to a TAD with the intent of identifying the clipped node and other/s sentinel nodes through a standard sentinel lymph node biopsy (SLNB). RESULTS: 54 patients and 55 axillary clipped nodes were included. The clip was intraoperatively encountered in every patient, accomplishing a 100% detection rate, although in one case no lymphatic tissue could be found in the intraoperative frozen section. An axillary lymph node dissection (ALND) was avoided in 62.9% of the cases (34/54). CONCLUSION: The use of the ROLL technique is a highly valuable tool since it allows a 100% success rate in retrieving the marker (and a 98.1% rate in detecting the clipped lymph node) in ycN0 breast cancer patients.

Cardiac sensitivity to rewards in cognitively inflexible nonclinical participants.

Background: In psychopathologies characterized by compulsive decision-making, core impairments include cognitive inflexibility and excessive sensitivity to rewards. It has been posited that traits shared by nonclinical individuals and psychiatric patients could help explain the pathogenesis of compulsive decision-making. Methods: To investigate whether cognitive inflexibility predisposes nonclinical individuals to poor choices and hyper-reactivity to reward, we recruited people with high and low scores for cognitive persistence and used the Iowa Gambling Task to assess decision-making and cardiac reactivity to monetary gains/losses. Results: As is frequently observed in psychophysiological research, the data indicated discrepancies among self-reports, behavior, and physiology. Cognitive inflexibility was not related to worse performance; however, monetary gains, in line with the literature, prompted marked cardiac accelerations. Consistent with our research goal, only inflexible participants showed large cardiac accelerations during the largest monetary wins. Discussion: Taken together, the data confirm an association between cognitive persistence and physiological reward sensitivity in a nonclinical population. The findings are in line with recent theories on the development of compulsive behaviors that consider cognitive inflexibility as a transdiagnostic impairment and predisposing factor for excessive reactivity to rewards, and might act both as a preexisting individual trait and drug-induced deficit.

Dual catalysis with an Ir(III)-Au(I) heterodimetallic complex: reduction of nitroarenes by transfer hydrogenation using primary alcohols.

A triazolyl-di-ylidene ligand has been used for the preparation of a homodimetallic complex of gold, and a heterodimetallic compound of gold and iridium. Both complexes have been fully characterized and their molecular structures have been determined by means of X-ray diffraction. The catalytic properties of these two complexes have been evaluated in the reduction of nitroarenes by transfer hydrogenation using primary alcohols. The two complexes afford different reaction products; whereas the Au(I)-Au(I) catalyst yields a hydroxylamine, the Ir(III)-Au(I) complex facilitates the formation of an imine.